This invention relates to novel immunosuppressive agents and a method for their production from syncytiotrophoblast microvilli membranes.
The syncytiotrophoblast is the outer syncytial layer of the trophoblast, which is an extraembryonic tissue that supplies nutrition to the embryo. The syncytiotrophoblast cell membrane has a large surface area due to microvillous folding of the membrane which communicates with the maternal blood lakes.
Increasing evidence indicates that local active suppression of the maternal immune response is important for foetal allograft survival. See Streilein and Wegmann, Immunol. Today 8, 362-366 (1987); Hunziker and Wegmann, CRC Critical Rev. Immunol. 6, 245-285 (1986); Chaouat and Monnot, Am. J. Reprod. Immunol. 6 , 5-8 (1984); Mowbray et al., Lancet, Apr. 27, 1985, pp. 941-943; Wegmann et al, Proc. Natl. Acad. Sci. USA 76, 2410-2414 (1979); and Jenkins et al., Brit. Med. J.1, 542-544 (1978).
Elucidation of a suppressive mechanism which allows maternal recognition of foetal antigens by the maternal immune response system without deleterious immunopathology would be a desirable goal.
Accordingly, isolation of immunosuppressive substances from placental sources would have significant value for understanding of both successful and unsuccessful (pre-eclampsia) foetal allografts and for the development of various immunosuppressive agents for therapeutic use.
An immunosuppressive glycoprotein termed uromodulin has been isolated heretofor from human pregnancy urine. Muchmore and Decker, Science 229, 474 (1985). Carbohydrate moieties derived from this glycoprotein were subsequently shown to be immunosuppressive in the absence of intact protein. Muchmore et al., J. Immunology 138, 2541-2546 (1987).